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2011 Grants - Ghiso

Abeta Catabolism and Its Impact in Alzheimer's Pathogenesis

Jorge A. Ghiso, Ph.D.
New York University School of Medicine
New York, New York

2011 Investigator-Initiated Research Grant

Beta-amyloid (also known as Abeta) is a protein fragment implicated in the development of Alzheimer's disease. When excessive amounts of beta-amyloid accumulate in the brain, they aggregate and form amyloid plaques, one of the hallmarks of Alzheimer's pathology. Scientists have been studying both the production and clearance of beta-amyloid in the brain to understand the causes of disease.

Jorge A. Ghiso, Ph.D. and colleagues have proposed to study the degradation and clearance of beta-amyloid from the brain using mice as a model system. They plan to inject labeled beta-amyloid into the mouse brain and study how enzymes in the brain degrade the protein fragment, and how this process is affected by aging. Dr. Ghiso and colleagues will also examine how deposits of beta-amyloid in brain blood vessels — also a common feature of Alzheimer's pathology — affect the ability of the brain to degrade and remove newly produced beta-amyloid fragments. For these latter studies, the researchers will use mice that have been genetically altered to exhibit amyloid deposits in different types of blood vessels. These studies will provide new insights into how the brain removes beta-amyloid, and they may suggest targets for new drug treatments to improve this process during aging.